Neuroprosthetic devices hold promise for future biomedical human-machine interactions. Various applications of this technology are actively being explored, ranging from direct neural control of prosthetic limbs to augmentation of sensory inputs. See, e.g., Andersen R A., et al. “Cognitive Neural Prosthetics.” Annu Rev Psychol. 2010; 61:169-C3; Venkatraman S, et al. “A System for Neural Recording and Closed-Loop Intracortical Microstimulation in Awake Rodents.” IEEE Transactions on Biomedical Engineering. 2009 January; 56(1):15-22. Indeed, first generation neuroprosthetics, such as cochlear implants, have already been used in the clinic (Fayad G and Elmiyeh B. “Cochlear Implant.” In: Hakim N S, editor. Artificial Organs. London: Springer London; 2009; p. 133-6). Despite this success, the long-term reliability of chronic cortical electrode implants remains a major obstacle to the widespread adaptation of neuroprosthetic technologies to the clinic, with many penetrating arrays losing the ability to record neurons after just weeks or months.
This lack of chronic reliability is often attributed to gliosis, the inflammatory response in the central nervous system. Gliosis is characterized by the formation of a glial scar around the implanted electrode in an attempt by the body to wall off the injury site from healthy tissue. A dense accumulation of microglia, macrophages, and reactive astrocytes produce extracellular matrix molecules that inhibit axonal growth within the scar. This encapsulation effectively increases the electrical impedance at the recording site, while also acting as a physical barrier between the electrode and the targeted neuronal populations. As the glial scar grows, the electrode becomes incapable of recording extracellular action potentials.
Bioelectrodes for neural recording and neurostimulation are an integral component of a number of neuroprosthetic devices, including commercially available cochlear implants and developmental devices, such as bionic eyes and brain-machine interfaces. Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD) and shows promise for the treatment of several other disorders, where it is essential to have a spatially precise contact between the electrode and tissue. Current rigid metal-based electrodes can acquire signals over a few days to weeks. However, continuing to extract signals with a high fidelity over long periods of time remains a major challenge. Presently, issues regarding electrode fracture and signal drop-out plague metal-based micro-electrodes for long-term use. Rigid metal needles do not comply mechanically with brain tissue, shifting during normal head movement, resulting in electrode misplacement from the target neural tissue area and electrode breaks.
The large mismatch between the elastic modulus of brain tissue and conventional silicon-based electrode shanks has been implicated as a significant factor contributing to chronic gliosis. Finite element analysis techniques have been used to model the large stress concentrations and “micromotion” effect that occur at the brain-electrode interface in response to indwelling, inelastic materials (Subbaroyan J. et al., “A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex.” Journal of Neural Engineering. 2005 Dec. 1; 2(4):103-13; Lee H, Bellamkonda R V. et al., “Biomechanical analysis of silicon microelectrode-induced strain in the brain.” Journal of Neural Engineering. 2005 Dec. 1; 2(4):81-9). Electrode micromotion resulting from a mismatch in stiffness between the electrode and the brain tissue leading to chronic inflammation and associated increased glial activation, and movement of the electrode from the target, resulting in inconsistent readings. Mechanical stress has been shown to stimulate astrocyte reactivity and neuronal death in vitro (Cullen D K et al., “Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal-astrocytic co-cultures.” Brain Research. 2007 Jul. 16; 1158(0):103-15), and in vivo studies have reported increased scarring around electrodes tethered to the skull, which are mechanically less compliant than free-floating probes (Thelin J, et al. “Implant Size and Fixation Mode Strongly Influence Tissue Reactions in the CNS.” PLoS ONE. 2011 Jan. 26; 6(1):e16267; Biran R. et al., “The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.” J Biomed Mater Res A. 2007 July; 82(1):169-78). A recent in vivo report compared the tissue response to stiff and compliant probes with the same surface chemistry, finding the compliant probes reduced glial scar intensity, with a greater density of nearby neurons compared to the stiff shanks at 4 weeks (Harris J P, et al. “Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies. Journal of Neural Engineering.” 2011 Oct. 1; 8:066011).
One approach to minimize electrode micromotion and associated glial scarring, and/or to provide strain relief at the electrode-issue interface is to use flexible, thin-film probes fabricated from polymers such as polyimide or parylene. See, e.g., Rousche P J, et al., “Flexible polyimide-based intracortical electrode arrays with bioactive capability.” Biomedical Engineering, IEEE Transactions on. 2001; 48(3):361-71; Mercanzini A, et al. “Demonstration of cortical recording using novel flexible polymer neural probes.” Sensors and Actuators A: Physical. 2008 May 2; 143(1):90-6; Hess A E, et al. “Development of a stimuli-responsive polymer nanocomposite toward biologically optimized, MEMS-based neural probes.” J. Micromech. Microeng. 2011 May; 21(5):054009; Kato Y. et al., “Preliminary Study of Multichannel Flexible Neural Probes Coated with Hybrid Biodegradable Polymer.” In: Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE. 2006. p. 660-3; Takeuchi S. et al. “Parylene flexible neural probes integrated with microfluidic channels.” Lab Chip. 2005 May; 5(5):519-23; Suzuki T, et al., “A 3D flexible parylene probe array for multichannel neural recording.” In: Neural Engineering, 2003. Conference Proceedings. First International IEEE EMBS Conference. 2003. p. 154-6; Wester B A, et al., “Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.” J. Neural Eng. 2009 April; 6(2):024002; and Seymour J P and Kipke D R. “Neural probe design for reduced tissue encapsulation in CNS.” Biomaterials. 2007 September; 28(25):3594-607. Such flexible probes introduce an additional challenge, however, as these devices can be incapable of penetrating the pia to achieve precise insertion into the brain without buckling.
Further, the neural recording interface remains another major challenge. Erosion of connections between the abiotic and biotic niches results in loss of function of electrodes and implants. This is an endemic problem in biology and one that has resisted traditional approaches for resolution. As a result, implants for recording electronics have relatively short lifetimes, requiring constant replacement, leading to associated failure modes due to the device itself or repeated surgical intervention that damages surrounding tissue.
Since most electrode implants remain relatively rigid and damaging upon insertion, the interface between current systems and the dynamic nature of biological systems tend to be a major source of problems. The dynamic issues include the biochemistry at the site (cell signaling factors, ECM deposition), cell dynamics at the site (e.g., astroglial and other nerve cells that respond to and with the implants), and stress shielding (e.g., mechanical mismatch between electrodes and soft brain tissue, leading to failure modes, fibrous encapsulation and related complications and failures to maintain a stable interface). Further, a related underlying problem includes the limited ability to establish a conformal and tight interface, due to the mechanical mismatch, between the existing materials and the soft and convoluted brain and neurological tissues. Therefore, there is a need to develop technologies and/or devices that can overcome one or more of the above limitations.